Intradermal naked plasmid DNA immunization: mechanisms of action

References

• Henri S, Guilliams M, Poulin LF et al. Disentangling the complexity of the skin dendritic cell network. Immunol. Cell Biol.88(4), 366–375 (2010).
   PubMedGoogle Scholar
• Romani N, Clausen BE, Stoitzner P. Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol. Rev.234(1), 120–141 (2010).
   PubMed Web of Science ®Google Scholar
• Meyer T, Stockfleth E, Christophers E. Immune response profiles in human skin. Br. J. Dermatol.157(Suppl. 2), 1–7 (2007).
   PubMedGoogle Scholar
• Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat. Rev. Immunol.9(10), 679–691 (2009).
   PubMed Web of Science ®Google Scholar
• Choi MJ, Maibach HI. Topical vaccination of DNA antigens: topical delivery of DNA antigens. Skin Pharmacol. Appl. Skin Physiol.16(5), 271–282 (2003).
   PubMedGoogle Scholar
• Peachman KK, Rao M, Alving CR. Immunization with DNA through the skin. Methods31(3), 232–242 (2003).
   PubMed Web of Science ®Google Scholar
• Tang DC, DeVit M, Johnston SA. Genetic immunization is a simple method for eliciting an immune response. Nature356(6365), 152–154 (1992).
   PubMed Web of Science ®Google Scholar
• Mumper RJ, Cui Z. Genetic immunization by jet injection of targeted pDNA-coated nanoparticles. Methods31(3), 255–262 (2003).
   PubMed Web of Science ®Google Scholar
• Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl Acad. Sci. USA90(24), 11478–11482 (1993).
   PubMed Web of Science ®Google Scholar
• Chen CH, Ji H, Suh KW, Choti MA, Pardoll DM, Wu TC. Gene gun-mediated DNA vaccination induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the liver and lungs. Gene Ther.6(12), 1972–1981 (1999).
   PubMed Web of Science ®Google Scholar
• Babiuk S, Baca-Estrada ME, Foldvari M et al. Electroporation improves the efficacy of DNA vaccines in large animals. Vaccine20(27–28), 3399–3408 (2002).
   PubMed Web of Science ®Google Scholar
• Selby M, Goldbeck C, Pertile T, Walsh R, Ulmer J. Enhancement of DNA vaccine potency by electroporation in vivo. J. Biotechnol.83(1–2), 147–152 (2000).
   PubMed Web of Science ®Google Scholar
• Widera G, Austin M, Rabussay D et al. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J. Immunol.164(9), 4635–4640 (2000).
   PubMed Web of Science ®Google Scholar
• Bins AD, Jorritsma A, Wolkers MC et al. A rapid and potent DNA vaccination strategy defined by in vivo monitoring of antigen expression. Nat. Med.11(8), 899–904 (2005).
   PubMed Web of Science ®Google Scholar
• Escobar-Chavez JJ, Bonilla-Martinez D, Villegas-Gonzalez MA, Molina-Trinidad E, Casas-Alancaster N, Revilla-Vazquez AL. Microneedles: a valuable physical enhancer to increase transdermal drug delivery. J. Clin. Pharmacol.51(7), 964–977 (2010).
   PubMedGoogle Scholar
• Coulman SA, Barrow D, Anstey A et al. Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Curr. Drug Deliv.3(1), 65–75 (2006).
   PubMedGoogle Scholar
• Raz E, Carson DA, Parker SE et al. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl Acad. Sci. USA91(20), 9519–9523 (1994).
   PubMed Web of Science ®Google Scholar
• Hengge UR, Walker PS, Vogel JC. Expression of naked DNA in human, pig, and mouse skin. J. Clin. Invest.97(12), 2911–2916 (1996).
   PubMed Web of Science ®Google Scholar
• Manthorpe M, Cornefert-Jensen F, Hartikka J et al. Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice. Hum. Gene Ther.4(4), 419–431 (1993).
   PubMed Web of Science ®Google Scholar
• Loke SL, Stein CA, Zhang XH et al. Characterization of oligonucleotide transport into living cells. Proc. Natl Acad. Sci. USA86(10), 3474–3478 (1989).
   PubMed Web of Science ®Google Scholar
• Benimetskaya L, Loike JD, Khaled Z et al. Mac-1 (CD11b/CD18) is an oligodeoxynucleotide-binding protein. Nat. Med.3(4), 414–420 (1997).
   PubMed Web of Science ®Google Scholar
• Basner-Tschakarjan E, Mirmohammadsadegh A, Baer A, Hengge UR. Uptake and trafficking of DNA in keratinocytes: evidence for DNA-binding proteins. Gene Ther.11(9), 765–774 (2004).
   PubMed Web of Science ®Google Scholar
• Laktionov PP, Dazard JE, Vives E et al. Characterisation of membrane oligonucleotide-binding proteins and oligonucleotide uptake in keratinocytes. Nucleic Acids Res.27(11), 2315–2324 (1999).
   PubMed Web of Science ®Google Scholar
• Budker V, Budker T, Zhang G, Subbotin V, Loomis A, Wolff JA. Hypothesis: naked plasmid DNA is taken up by cells in vivo by a receptor-mediated process. J. Gene Med.2(2), 76–88 (2000).
   PubMed Web of Science ®Google Scholar
• Wittrup A, Sandgren S, Lilja J et al. Identification of proteins released by mammalian cells that mediate DNA internalization through proteoglycan-dependent macropinocytosis. J. Biol. Chem.282(38), 27897–27904 (2007).
   PubMedGoogle Scholar
• Lechardeur D, Lukacs GL. Intracellular barriers to non-viral gene transfer. Curr. Gene Ther.2(2), 183–194 (2002).
   PubMedGoogle Scholar
• Lam AP, Dean DA. Progress and prospects: nuclear import of nonviral vectors. Gene Ther.17(4), 439–447 (2010).
   PubMed Web of Science ®Google Scholar
• Wolff JA, Budker V. The mechanism of naked DNA uptake and expression. Adv. Genet.54, 3–20 (2005).
   PubMed Web of Science ®Google Scholar
• Bevan MJ. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J. Exp. Med.143(5), 1283–1288 (1976).
   PubMed Web of Science ®Google Scholar
• Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: a review. Crit. Rev. Immunol.18(5), 389–418 (1998).
   PubMed Web of Science ®Google Scholar
• Zhu FG, Reich CF, Pisetsky DS. The role of the macrophage scavenger receptor in immune stimulation by bacterial DNA and synthetic oligonucleotides. Immunology103(2), 226–234 (2001).
   PubMed Web of Science ®Google Scholar
• Rottembourg D, Filippi CM, Bresson D et al. Essential role for TLR9 in prime but not prime–boost plasmid DNA vaccination to activate dendritic cells and protect from lethal viral infection. J. Immunol.184(12), 7100–7107 (2010).
   PubMed Web of Science ®Google Scholar
• Pavlenko M, Leder C, Moreno S, Levitsky V, Pisa P. Priming of CD8+ T-cell responses after DNA immunization is impaired in TLR9- and MyD88-deficient mice. Vaccine25(34), 6341–6347 (2007).
   PubMed Web of Science ®Google Scholar
• Sato Y, Roman M, Tighe H et al. Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science273(5273), 352–354 (1996).
   PubMed Web of Science ®Google Scholar
• Unterholzner L, Keating SE, Baran M et al. IFI16 is an innate immune sensor for intracellular DNA. Nat. Immunol.11(11), 997–1004 (2010).
   PubMed Web of Science ®Google Scholar
• Spies B, Hochrein H, Vabulas M et al. Vaccination with plasmid DNA activates dendritic cells via Toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice. J. Immunol.171(11), 5908–5912 (2003).
   PubMed Web of Science ®Google Scholar
• Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov.5(6), 471–484 (2006).
   PubMed Web of Science ®Google Scholar
• Hornung V, Ablasser A, Charrel-Dennis M et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature458(7237), 514–518 (2009).
   PubMed Web of Science ®Google Scholar
• Babiuk S, Mookherjee N, Pontarollo R et al. TLR9-/- and TLR9+/+ mice display similar immune responses to a DNA vaccine. Immunology113(1), 114–120 (2004).
   PubMed Web of Science ®Google Scholar
• Heath WR, Carbone FR. Dendritic cell subsets in primary and secondary T cell responses at body surfaces. Nat. Immunol.10(12), 1237–1244 (2009).
   PubMed Web of Science ®Google Scholar
• Bennett CL, Clausen BE. DC ablation in mice: promises, pitfalls, and challenges. Trends Immunol.28(12), 525–531 (2007).
   PubMed Web of Science ®Google Scholar
• Allan RS, Smith CM, Belz GT et al. Epidermal viral immunity induced by CD8α+ dendritic cells but not by Langerhans cells. Science301(5641), 1925–1928 (2003).
   PubMed Web of Science ®Google Scholar
• Iezzi G, Frohlich A, Ernst B et al. Lymph node resident rather than skin-derived dendritic cells initiate specific T cell responses after Leishmania major infection. J. Immunol.177(2), 1250–1256 (2006).
   PubMed Web of Science ®Google Scholar
• He Y, Zhang J, Donahue C, Falo LD Jr. Skin-derived dendritic cells induce potent CD8(+) T cell immunity in recombinant lentivector-mediated genetic immunization. Immunity24(5), 643–656 (2006).
   PubMed Web of Science ®Google Scholar
• Allan RS, Waithman J, Bedoui S et al. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity25(1), 153–162 (2006).
   PubMed Web of Science ®Google Scholar
• Bursch LS, Wang L, Igyarto B et al. Identification of a novel population of langerin+ dendritic cells. J. Exp. Med.204(13), 3147–3156 (2007).
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Collin MP, Bogunovic M et al. Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state. J. Exp. Med.204(13), 3133–3146 (2007).
   PubMed Web of Science ®Google Scholar
• Merad M, Ginhoux F, Collin M. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol.8(12), 935–947 (2008).
   PubMed Web of Science ®Google Scholar
• Poulin LF, Henri S, de Bovis B, Devilard E, Kissenpfennig A, Malissen B. The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. J. Exp. Med.204(13), 3119–3131 (2007).
   PubMed Web of Science ®Google Scholar
• Nagao K, Ginhoux F, Leitner WW et al. Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions. Proc. Natl Acad. Sci. USA106(9), 3312–3317 (2009).
   PubMed Web of Science ®Google Scholar
• Bedoui S, Whitney PG, Waithman J et al. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat. Immunol.10(5), 488–495 (2009).
   PubMed Web of Science ®Google Scholar
• Sille FC, Visser A, Boes M. T cell priming by tissue-derived dendritic cells: new insights from recent murine studies. Cell Immunol.237(2), 77–85 (2005).
   PubMed Web of Science ®Google Scholar
• Miller LS, Sorensen OE, Liu PT et al. TGF-α regulates TLR expression and function on epidermal keratinocytes. J. Immunol.174(10), 6137–6143 (2005).
   PubMed Web of Science ®Google Scholar
• Mempel M, Voelcker V, Kollisch G et al. Toll-like receptor expression in human keratinocytes: nuclear factor κB controlled gene activation by Staphylococcus aureus is Toll-like receptor 2 but not Toll-like receptor 4 or platelet activating factor receptor dependent. J. Invest. Dermatol.121(6), 1389–1396 (2003).
   PubMedGoogle Scholar
• Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol. Rev.223, 20–38 (2008).
   PubMed Web of Science ®Google Scholar
• Elnekave M, Furmanov K, Nudel I, Arizon M, Clausen BE, Hovav AH. Directly transfected langerin+ dermal dendritic cells potentiate CD8+ T cell responses following intradermal plasmid DNA immunization. J. Immunol.185(6), 3463–3471 (2010).
   PubMedGoogle Scholar
• Gilliet M, Lande R. Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Curr. Opin. Immunol.20(4), 401–407 (2008).
   PubMed Web of Science ®Google Scholar
• Clark RA. Skin-resident T cells: the ups and downs of on site immunity. J. Invest. Dermatol.130(2), 362–370 (2010).
   PubMed Web of Science ®Google Scholar
• Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol.10(5), 524–530 (2009).
   PubMed Web of Science ®Google Scholar
• Wakim LM, Waithman J, van Rooijen N, Heath WR, Carbone FR. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science319(5860), 198–202 (2008).
   PubMed Web of Science ®Google Scholar
• Girardi M, Oppenheim DE, Steele CR et al. Regulation of cutaneous malignancy by γδ T cells. Science294(5542), 605–609 (2001).
   PubMed Web of Science ®Google Scholar
• Strid J, Tigelaar RE, Hayday AC. Skin immune surveillance by T cells – a new order? Semin. Immunol.21(3), 110–120 (2009).
   PubMedGoogle Scholar
• Girardi M. Immunosurveillance and immunoregulation by γδ T cells. J. Invest. Dermatol.126(1), 25–31 (2006).
   PubMed Web of Science ®Google Scholar
• Forg P, von Hoegen P, Dalemans W, Schirrmacher V. Superiority of the ear pinna over muscle tissue as site for DNA vaccination. Gene Ther.5(6), 789–797 (1998).
   PubMed Web of Science ®Google Scholar
• Hovav AH, Panas MW, Rahman S et al. Duration of antigen expression in vivo following DNA immunization modifies the magnitude, contraction, and secondary responses of CD8+ T lymphocytes. J. Immunol.179(10), 6725–6733 (2007).
   PubMed Web of Science ®Google Scholar
• Akbari O, Panjwani N, Garcia S, Tascon R, Lowrie D, Stockinger B. DNA vaccination: transfection and activation of dendritic cells as key events for immunity. J. Exp. Med.189(1), 169–178 (1999).
   PubMed Web of Science ®Google Scholar
• Roos AK, Eriksson F, Walters DC, Pisa P, King AD. Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients. Mol. Ther.17(9), 1637–1642 (2009).
   PubMed Web of Science ®Google Scholar
• Geiben-Lynn R, Greenland JR, Frimpong-Boateng K, van Rooijen N, Hovav AH, Letvin NL. CD4+ T lymphocytes mediate in vivo clearance of plasmid DNA vaccine antigen expression and potentiate CD8+ T-cell immune responses. Blood112(12), 4585–4590 (2008).
   PubMed Web of Science ®Google Scholar
• Greenland JR, Geiben R, Ghosh S, Pastor WA, Letvin NL. Plasmid DNA vaccine-elicited cellular immune responses limit in vivo vaccine antigen expression through Fas-mediated apoptosis. J. Immunol.178(9), 5652–5658 (2007).
   PubMedGoogle Scholar
• Payette PJ, Weeratna RD, McCluskie MJ, Davis HL. Immune-mediated destruction of transfected myocytes following DNA vaccination occurs via multiple mechanisms. Gene Ther.8(18), 1395–1400 (2001).
   PubMedGoogle Scholar
• Brooks AR, Harkins RN, Wang P, Qian HS, Liu P, Rubanyi GM. Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle. J. Gene Med.6(4), 395–404 (2004).
   PubMed Web of Science ®Google Scholar
• Vanniasinkam T, Ertl H, Tang Q. Trichostatin-A enhances adaptive immune responses to DNA vaccination. J. Clin. Virol.36(4), 292–297 (2006).
   PubMedGoogle Scholar
• Geiben-Lynn R, Greenland JR, Frimpong-Boateng K, Letvin NL. Non-classical natural killer T cells modulate plasmid DNA vaccine antigen expression and vaccine-elicited immune responses by MCP-1 secretion after interaction with a β2-microglobulin-independent CD1d. J. Biol. Chem.284(49), 33800–33806 (2009).
   PubMed Web of Science ®Google Scholar
• Bot A, Stan AC, Inaba K, Steinman R, Bona C. Dendritic cells at a DNA vaccination site express the encoded influenza nucleoprotein and prime MHC class I-restricted cytolytic lymphocytes upon adoptive transfer. Int. Immunol.12(6), 825–832 (2000).
   PubMedGoogle Scholar
• Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA. Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J. Exp. Med.186(9), 1481–1486 (1997).
   PubMed Web of Science ®Google Scholar
• Bouloc A, Walker P, Grivel JC, Vogel JC, Katz SI. Immunization through dermal delivery of protein-encoding DNA: a role for migratory dendritic cells. Eur. J. Immunol.29(2), 446–454 (1999).
   PubMed Web of Science ®Google Scholar
• Tuomela M, Malm M, Wallen M, Stanescu I, Krohn K, Peterson P. Biodistribution and general safety of a naked DNA plasmid, GTU-MultiHIV, in a rat, using a quantitative PCR method. Vaccine23(7), 890–896 (2005).
   PubMedGoogle Scholar
• Bedoui S, Davey GM, Lew AM, Heath WR. Equivalent stimulation of naive and memory CD8 T cells by DNA vaccination: a dendritic cell-dependent process. Immunol. Cell Biol.87(3), 255–259 (2009).
   PubMedGoogle Scholar
• Hon H, Oran A, Brocker T, Jacob J. B lymphocytes participate in cross-presentation of antigen following gene gun vaccination. J. Immunol.174(9), 5233–5242 (2005).
   PubMed Web of Science ®Google Scholar
• Corr M, von Damm A, Lee DJ, Tighe H. In vivo priming by DNA injection occurs predominantly by antigen transfer. J. Immunol.163(9), 4721–4727 (1999).
   PubMed Web of Science ®Google Scholar
• Vandermeulen G, Richiardi H, Escriou V et al. Skin-specific promoters for genetic immunisation by DNA electroporation. Vaccine27(32), 4272–4277 (2009).
   PubMed Web of Science ®Google Scholar
• Cho JH, Youn JW, Sung YC. Cross-priming as a predominant mechanism for inducing CD8(+) T cell responses in gene gun DNA immunization. J. Immunol.167(10), 5549–5557 (2001).
   PubMed Web of Science ®Google Scholar
• Lauterbach H, Gruber A, Ried C, Cheminay C, Brocker T. Insufficient APC capacities of dendritic cells in gene gun-mediated DNA vaccination. J. Immunol.176(8), 4600–4607 (2006).
   PubMedGoogle Scholar
• Furmanov K, Elnekave M, Lehmann D, Clausen BE, Kotton DN, Hovav AH. The role of skin-derived dendritic cells in CD8+ T cell priming following immunization with lentivectors. J. Immunol.184(9), 4889–4897 (2010).
   PubMedGoogle Scholar
• Brewig N, Kissenpfennig A, Malissen B et al. Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes. J. Immunol.182(2), 774–783 (2009).
   PubMedGoogle Scholar
• Noordegraaf M, Flacher V, Stoitzner P, Clausen BE. Functional redundancy of Langerhans cells and langerin(+) dermal dendritic cells in contact hypersensitivity. J. Invest. Dermatol.130(12), 2752–2759 (2010).
   PubMedGoogle Scholar
• Stoecklinger A, Grieshuber I, Scheiblhofer S et al. Epidermal Langerhans cells are dispensable for humoral and cell-mediated immunity elicited by gene gun immunization. J. Immunol.179(2), 886–893 (2007).
   PubMed Web of Science ®Google Scholar
• Stoecklinger A, Eticha TD, Mesdaghi M et al. Langerin+ dermal dendritic cells are critical for CD8+ T cell activation and IgH γ-1 class switching in response to gene gun vaccines. J. Immunol.186(3), 1377–1383 (2011).
   PubMed Web of Science ®Google Scholar
• Clausen BE, Kel JM. Langerhans cells: critical regulators of skin immunity? Immunol. Cell Biol.88(4), 351–360 (2010).
   PubMed Web of Science ®Google Scholar
• Nudel I, Elnekave M, Furmanov K et al. Dendritic cells in distinct oral mucosal tissues engage different mechanisms to prime CD8+ T cells. J. Immunol.186(2), 891–900 (2011).
   PubMedGoogle Scholar
• Henri S, Poulin LF, Tamoutounour S et al. CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. J. Exp. Med.207(1), 189–206 (2010).
   PubMed Web of Science ®Google Scholar
• Sugita K, Kabashima K, Atarashi K, Shimauchi T, Kobayashi M, Tokura Y. Innate immunity mediated by epidermal keratinocytes promotes acquired immunity involving Langerhans cells and T cells in the skin. Clin. Exp. Immunol.147(1), 176–183 (2007).
   PubMed Web of Science ®Google Scholar
• Stoitzner P, Tripp CH, Eberhart A et al. Langerhans cells cross-present antigen derived from skin. Proc. Natl Acad. Sci. USA103(20), 7783–7788 (2006).
   PubMed Web of Science ®Google Scholar
• Jelley-Gibbs DM, Brown DM, Dibble JP, Haynes L, Eaton SM, Swain SL. Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J. Exp. Med.202(5), 697–706 (2005).
   PubMed Web of Science ®Google Scholar
• Turner DL, Cauley LS, Khanna KM, Lefrancois L. Persistent antigen presentation after acute vesicular stomatitis virus infection. J. Virol.81(4), 2039–2046 (2007).
   PubMed Web of Science ®Google Scholar
• Zammit DJ, Turner DL, Klonowski KD, Lefrancois L, Cauley LS. Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity24(4), 439–449 (2006).
   PubMed Web of Science ®Google Scholar
• Barber DL, Wherry EJ, Masopust D et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature439(7077), 682–687 (2006).
   PubMed Web of Science ®Google Scholar
• Halwani R, Boyer JD, Yassine-Diab B et al. Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA + IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques. J. Immunol.180(12), 7969–7979 (2008).
   PubMed Web of Science ®Google Scholar
• Velu V, Kannanganat S, Ibegbu C et al. Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination. J. Virol.81(11), 5819–5828 (2007).
   PubMedGoogle Scholar
• Smith KA, Tam VL, Wong RM et al. Enhancing DNA vaccination by sequential injection of lymph nodes with plasmid vectors and peptides. Vaccine27(19), 2603–2615 (2009).
   PubMed Web of Science ®Google Scholar
• Bot A, Qiu Z, Wong R, Obrocea M, Smith KA. Programmed cell death-1 (PD-1) at the heart of heterologous prime–boost vaccines and regulation of CD8+ T cell immunity. J. Transl. Med.8, 132 (2010).
   PubMedGoogle Scholar
• Mueller SN, Jones CM, Smith CM, Heath WR, Carbone FR. Rapid cytotoxic T lymphocyte activation occurs in the draining lymph nodes after cutaneous herpes simplex virus infection as a result of early antigen presentation and not the presence of virus. J. Exp. Med.195(5), 651–656 (2002).
   PubMedGoogle Scholar
• Norbury CC, Malide D, Gibbs JS, Bennink JR, Yewdell JW. Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat. Immunol.3(3), 265–271 (2002).
   PubMed Web of Science ®Google Scholar
• Liu L, Fuhlbrigge RC, Karibian K, Tian T, Kupper TS. Dynamic programming of CD8+ T cell trafficking after live viral immunization. Immunity25(3), 511–520 (2006).
   PubMedGoogle Scholar
• Klinman DM, Sechler JM, Conover J, Gu M, Rosenberg AS. Contribution of cells at the site of DNA vaccination to the generation of antigen-specific immunity and memory. J. Immunol.160(5), 2388–2392 (1998).
   PubMed Web of Science ®Google Scholar
• Torres CA, Iwasaki A, Barber BH, Robinson HL. Differential dependence on target site tissue for gene gun and intramuscular DNA immunizations. J. Immunol.158(10), 4529–4532 (1997).
   PubMed Web of Science ®Google Scholar
• van den Berg JH, Nujien B, Beijnen JH et al. Optimization of intradermal vaccination by DNA tattooing in human skin. Hum. Gene Ther.20(3), 181–189 (2009).
   PubMed Web of Science ®Google Scholar
• Yoshida A, Nagata T, Uchijima M, Koide Y. Protective CTL response is induced in the absence of CD4+ T cells and IFN-γ by gene gun DNA vaccination with a minigene encoding a CTL epitope of Listeria monocytogenes. Vaccine19(30), 4297–4306 (2001).
   PubMed Web of Science ®Google Scholar
• Hawkins WG, Gold JS, Dyall R et al. Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity. Surgery128(2), 273–280 (2000).
   PubMed Web of Science ®Google Scholar
• Maecker HT, Umetsu DT, DeKruyff RH, Levy S. Cytotoxic T cell responses to DNA vaccination: dependence on antigen presentation via class II MHC. J. Immunol.161(12), 6532–6536 (1998).
   PubMedGoogle Scholar
• Wild J, Grusby MJ, Schirmbeck R, Reimann J. Priming MHC-I-restricted cytotoxic T lymphocyte responses to exogenous hepatitis B surface antigen is CD4+ T cell dependent. J. Immunol.163(4), 1880–1887 (1999).
   PubMed Web of Science ®Google Scholar
• Chan K, Lee DJ, Schubert A et al. The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA. J. Immunol.166(5), 3061–3066 (2001).
   PubMedGoogle Scholar
• Corr M, Tighe H, Lee D et al. Costimulation provided by DNA immunization enhances antitumor immunity. J. Immunol.159(10), 4999–5004 (1997).
   PubMed Web of Science ®Google Scholar
• Obst R, van Santen HM, Mathis D, Benoist C. Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response. J. Exp. Med.201(10), 1555–1565 (2005).
   PubMedGoogle Scholar
• Badovinac VP, Porter BB, Harty JT. Programmed contraction of CD8(+) T cells after infection. Nat. Immunol.3(7), 619–626 (2002).
   PubMed Web of Science ®Google Scholar
• Koup RA, Roederer M, Lamoreaux L et al. Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses. PLoS ONE5(2), e9015 (2010).
   PubMed Web of Science ®Google Scholar
• Jaoko W, Karita E, Kayitenkore K et al. Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa. PLoS ONE5(9), e12873 (2010).
   PubMed Web of Science ®Google Scholar
• Santra S, Liao HX, Zhang R et al. Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys. Nat. Med.16(3), 324–328 (2010).
   PubMed Web of Science ®Google Scholar
• Gilbert SC, Moorthy VS, Andrews L et al. Synergistic DNA-MVA prime–boost vaccination regimes for malaria and tuberculosis. Vaccine24(21), 4554–4561 (2006).
   PubMed Web of Science ®Google Scholar
• Hovav AH, Panas MW, Osuna CE, Cayabyab MJ, Autissier P, Letvin NL. The impact of a boosting immunogen on the differentiation of secondary memory CD8+ T cells. J. Virol.81(23), 12793–12802 (2007).
   PubMed Web of Science ®Google Scholar
• Santra S, Barouch DH, Korioth-Schmitz B et al. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses. Proc. Natl Acad. Sci. USA101(30), 11088–11093 (2004).
   PubMed Web of Science ®Google Scholar
• Richmond JF, Lu S, Santoro JC et al. Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting. J. Virol.72(11), 9092–9100 (1998).
   PubMed Web of Science ®Google Scholar
• Richmond JF, Mustafa F, Lu S et al. Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting. Virology230(2), 265–274 (1997).
   PubMedGoogle Scholar
• Fuller DH, Simpson L, Cole KS et al. Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV. Immunol. Cell Biol.75(4), 389–396 (1997).
   PubMed Web of Science ®Google Scholar
• Degano P, Schneider J, Hannan CM, Gilbert SC, Hill AV. Gene gun intradermal DNA immunization followed by boosting with modified vaccinia virus Ankara: enhanced CD8+ T cell immunogenicity and protective efficacy in the influenza and malaria models. Vaccine18(7–8), 623–632 (1999).
   PubMed Web of Science ®Google Scholar
• Radcliffe JN, Roddick JS, Friedmann PS, Stevenson FK, Thirdborough SM. Prime–boost with alternating DNA vaccines designed to engage different antigen presentation pathways generates high frequencies of peptide-specific CD8+ T cells. J. Immunol.177(10), 6626–6633 (2006).
   PubMed Web of Science ®Google Scholar
• Kim TW, Lee JH, He L, Boyd DA, Hung CF, Wu TC. DNA vaccines employing intracellular targeting strategies and a strategy to prolong dendritic cell life generate a higher number of CD8+ memory T cells and better long-term antitumor effects compared with a DNA prime–vaccinia boost regimen. Hum. Gene Ther.16(1), 26–34 (2005).
   PubMedGoogle Scholar
• Brice GT, Dobano C, Sedegah M et al. Extended immunization intervals enhance the immunogenicity and protective efficacy of plasmid DNA vaccines. Microbes Infect.9(12–13), 1439–1446 (2007).
   PubMed Web of Science ®Google Scholar
• Belz GT, Bedoui S, Kupresanin F, Carbone FR, Heath WR. Minimal activation of memory CD8+ T cell by tissue-derived dendritic cells favors the stimulation of naive CD8+ T cells. Nat. Immunol.8(10), 1060–1066 (2007).
   PubMed Web of Science ®Google Scholar
• Radcliffe JN, Roddick JS, Stevenson FK, Thirdborough SM. Prolonged antigen expression following DNA vaccination impairs effector CD8+ T cell function and memory development. J. Immunol.179(12), 8313–8321 (2007).
   PubMedGoogle Scholar
• Wherry EJ, Barber DL, Kaech SM, Blattman JN, Ahmed R. Antigen-independent memory CD8 T cells do not develop during chronic viral infection. Proc. Natl Acad. Sci. USA101(45), 16004–16009 (2004).
   PubMed Web of Science ®Google Scholar
• Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature401(6754), 708–712 (1999).
   PubMed Web of Science ®Google Scholar
• Elnekave M, Bivas-Benita M, Gillard GO, Sircar P, Hovav AH. A matter of timing: unsynchronized antigen expression and antigen presentation diminish secondary T cell responses. J. Immunol.183(2), 1013–1021 (2009).
   PubMedGoogle Scholar
• Endmann A, Baden M, Weisermann E et al. Immune response induced by a linear DNA vector: influence of dose, formulation and route of injection. Vaccine28(21), 3642–3649 (2010).
   PubMedGoogle Scholar
• Kurupati P, Ramachandran NP, Poh CL. Protective efficacy of DNA vaccines encoding outer membrane protein A and OmpK36 of Klebsiella pneumoniae in mice. Clin. Vaccine Immunol.18(1), 82–88 (2011).
   PubMed Web of Science ®Google Scholar
• Osinubi MO, Wu X, Franka R et al. Enhancing comparative rabies DNA vaccine effectiveness through glycoprotein gene modifications. Vaccine27(51), 7214–7218 (2009).
   PubMed Web of Science ®Google Scholar
• Lodmell DL, Ewalt LC, Parnell MJ, Rupprecht CE, Hanlon CA. One-time intradermal DNA vaccination in ear pinnae one year prior to infection protects dogs against rabies virus. Vaccine24(4), 412–416 (2006).
   PubMedGoogle Scholar
• Gaffal E, Schweichel D, Tormo D et al. Comparative evaluation of CD8+CTL responses following gene gun immunization targeting the skin with intracutaneous injection of antigen-transduced dendritic cells. Eur. J. Cell Biol.86(11–12), 817–826 (2007).
   PubMedGoogle Scholar
• Garg S, Oran A, Wajchman J et al. Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo. Nat. Immunol.4(9), 907–912 (2003).
   PubMedGoogle Scholar
• Dondji B, Deak E, Goldsmith-Pestana K et al. Intradermal NKT cell activation during DNA priming in heterologous prime–boost vaccination enhances T cell responses and protection against Leishmania. Eur. J. Immunol.38(3), 706–719 (2008).
   PubMedGoogle Scholar
• Minigo G, Scholzen A, Tang CK et al. Poly-L-lysine-coated nanoparticles: a potent delivery system to enhance DNA vaccine efficacy. Vaccine25(7), 1316–1327 (2007).
   PubMed Web of Science ®Google Scholar
• Kawase A, Isaji K, Yamaoka A, Kobayashi N, Nishikawa M, Takakura Y. Enhanced antigen-specific antibody production following polyplex-based DNA vaccination via the intradermal route in mice. Vaccine24(27–28), 5535–5545 (2006).
   PubMed Web of Science ®Google Scholar
• Schwendener RA, Ludewig B, Cerny A, Engler O. Liposome-based vaccines. Methods Mol. Biol.605, 163–175 (2010).
   PubMedGoogle Scholar
• Manoj S, Griebel PJ, Babiuk LA, van Drunen Littel-van den Hurk S. Modulation of immune responses to bovine herpesvirus-1 in cattle by immunization with a DNA vaccine encoding glycoprotein D as a fusion protein with bovine CD154. Immunology112(2), 328–338 (2004).
   PubMedGoogle Scholar
• Melkebeek V, Verdonck F, Stuyven E, Goddeeris B, Cox E. Plasmid-encoded GM-CSF induces priming of the F4(K88)-specific serum IgA response by FaeG DNA vaccination in pigs. Vaccine24(21), 4592–4594 (2006).
   PubMedGoogle Scholar
• Gartner T, Romano M, Suin V et al. Immunogenicity and protective efficacy of a tuberculosis DNA vaccine co-expressing pro-apoptotic caspase-3. Vaccine26(11), 1458–1470 (2008).
   PubMed Web of Science ®Google Scholar
• Geiben-Lynn R, Frimpong-Boateng K, Letvin NL. Modulation of plasmid DNA vaccine antigen clearance by caspase 12 RNA interference (RNAi) potentiates vaccination. Clin. Vaccine Immunol.18(4), 533–538 (2011).
   PubMed Web of Science ®Google Scholar
• Parsania M, Bamdad T, Hassan ZM et al. Evaluation of apoptotic and anti-apoptotic genes on efficacy of DNA vaccine encoding glycoprotein B of herpes simplex virus type 1. Immunol. Lett.128(2), 137–142 (2010).
   PubMedGoogle Scholar
• Kim JH, Chen J, Majumder N, Lin H, Falo LD Jr, You Z. ‘Survival gene’ Bcl-xl potentiates DNA-raised antitumor immunity. Gene Ther.12(20), 1517–1525 (2005).
   PubMedGoogle Scholar
• Kim TW, Hung CF, Ling M et al. Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins. J. Clin. Invest.112(1), 109–117 (2003).
   PubMed Web of Science ®Google Scholar
• Hon H, Rucker EB 3rd, Hennighausen L, Jacob J. bcl-xl is critical for dendritic cell survival in vivo. J. Immunol.173(7), 4425–4432 (2004).
   PubMed Web of Science ®Google Scholar
• Holst PJ, Bassi MR, Thomsen AR, Christensen JP. DNA fusion gene vaccines. Curr. Opin. Mol. Ther.12(1), 47–54 (2010).
   PubMedGoogle Scholar
• Huang Y, Babiuk LA, van Drunen Littel-van den Hurk S. The cell-mediated immune response induced by plasmid encoding bovine herpesvirus 1 glycoprotein B is enhanced by plasmid encoding IL-12 when delivered intramuscularly or by gene gun, but not after intradermal injection. Vaccine24(25), 5349–5359 (2006).
   PubMedGoogle Scholar
• Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat. Rev. Genet.9(10), 776–788 (2008).
   PubMed Web of Science ®Google Scholar
• Nchinda G, Kuroiwa J, Oks M et al. The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. J. Clin. Invest.118(4), 1427–1436 (2008).
   PubMed Web of Science ®Google Scholar
• Demangel C, Zhou J, Choo AB, Shoebridge G, Halliday GM, Britton WJ. Single chain antibody fragments for the selective targeting of antigens to dendritic cells. Mol. Immunol.42(8), 979–985 (2005).
   PubMedGoogle Scholar
• Grossmann C, Tenbusch M, Nchinda G et al. Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic Toll-like receptor ligands. BMC Immunol.10, 43 (2009).
   PubMed Web of Science ®Google Scholar